ßblockers inhibit the viability of breast cancer cells by regulating the ERK/COX2 signaling pathway and the drug response is affected by ADRB2 singlenucleotide polymorphisms.
Oncol Rep
; 41(1): 341-350, 2019 Jan.
Article
in En
| MEDLINE
| ID: mdl-30542705
ABSTRACT
The ß2adrenergic receptor (ß2AR, encoded by the ADRB2 gene) is a member of the Gproteincoupled receptor superfamily that can be stimulated by catecholamines. Studies in vivo and in vitro have confirmed that ßblockers (ßAR antagonists) exert antitumor effects on various tumors. Furthermore, ADRB2 singlenucleotide polymorphisms (SNPs) have been identified to alter the expression and conformation of ß2AR, which may alter the ßblocker drug response. The aim of the present study was to investigate the effect of ßblockers on triplenegative breast cancer cells and determine whether ADRB2 SNPs affect the response to ßblocker drugs. Propranolol and ICI 118,551 significantly inhibited the viability of MDAMB231 cells, arrested cell cycle progression at G0/G1 and S phase and induced cell apoptosis. Western blot analysis indicated that the phosphorylation levels of extracellularsignalregulated kinase (ERK)1/2 and the expression levels of cyclooxygenase 2 (COX2) were significantly decreased following ßblocker treatment. Four haplotypes, which comprised ADRB2 SNPs rs1042713 and rs1042714, were transfected into 293 cells. After 24 and 48 h of transfection, ADRB2 mRNA expression was significantly decreased in mutant groups compared with the wildtype group. The ADRB2 SNPs exerted no effect on cell viability, but did affect the drug response of ICI 118,551. Furthermore, ADRB2 SNPs also affected the regulatory function of ICI 118,551 on the ERK/COX2 signaling pathway. Collectively, propranolol and ICI 118,551 inhibited the viability of MDAMB231 cells by downregulating the ERK/COX2 signaling pathway and inducing apoptosis. The results of the present study indicated that SNPs rs1042713 and rs1042714 of ADRB2 affected the response to ICI 118,551, and the underlying molecular mechanism was elucidated.
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Signal Transduction
/
Receptors, Adrenergic, beta-2
/
Adrenergic beta-Antagonists
/
Triple Negative Breast Neoplasms
Limits:
Humans
Language:
En
Journal:
Oncol Rep
Year:
2019
Document type:
Article